2-(Dicyclohexylphosphino)biphenyl → N2-(3-Methoxy-4-(6-methylpyridazin-4-yl)phenyl)-N4-methyl-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidine-2,4-diamine

HRID 59153

Reaction equation

HRID 59153 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[CH:5]=[C:4]([CH2:10][O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[N:3]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][C:25]=1[C:26]1[CH:31]=[C:30]([CH3:32])[N:29]=[N:28][CH:27]=1)[NH2:22].[Cs].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[N:7]=[C:6]([NH:8][CH3:9])[CH:5]=[C:4]([CH2:10][O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[N:3]=2)[CH:23]=[CH:24][C:25]=1[C:26]1[CH:31]=[C:30]([CH3:32])[N:29]=[N:28][CH:27]=1

Participants

7

Reactant 4

HCID 27342162-(Dicyclohexylphosphino)biphenyl2×HCID 5354618CesiumHCID 668590663-Methoxy-4-(6-methylpyridazin-4-yl)anilineHCID 1178212102-Chloro-N-methyl-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-amine2×

Product 1

HCID 86344800N2-(3-Methoxy-4-(6-methylpyridazin-4-yl)phenyl)-N4-methyl-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-N-methyl-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-amine (50 mg, 0.20 mmol), 3-methoxy-4-(6-methylpyridazin-4-yl)aniline (42 mg, 0.20 mmol), cesium rbonate (127 mg, 0.39 mmol), palladium (II) acetate (7 mg, 0.03 mmol) and 2-(dicyclohexylphosphino)-biphenyl (10 mg, 0.03 mmol) in dioxane (2 mL) was heated under argon at 120° C. for 90 minutes in a microwave reactor. 2-Chloro-N-methyl-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-amine (72 mg, 0.28 mmol, 1.4 eq), palladium(II) acetate (7 mg) and 2-(dicyclohexylphosphino)biphenyl (10 mg) was added and the mixture was heated at 120° C. for 90 minutes in a microwave reactor. The mixture was filtered through a short silica gel plug which was washed with 10% solution of methanol in ethyl acetate (75 mL). The eluate was concentrated in vacuum and the residue was purified by preparative to give the title compound as a solid, 22 mg (26%).

Workup

  1. temperaturethe mixture was heated at 120° C. for 90 minutes in a microwave reactor
  2. filtrationThe mixture was filtered through a short silica gel plug which
  3. washwas washed with 10% solution of methanol in ethyl acetate (75 mL)
  4. concentrationThe eluate was concentrated in vacuum
  5. customthe residue was purified by preparative

Sources & evidence

ORD record
ord-766617a20112464390c873db4aff3d00
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Linked notes

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